Is Fezakinumab, an anti-IL22 antibody, a putative novel therapy for a subset of severe asthma?

<b>Background:</b> Antibody-based therapies against Type 2 targets have been introduced for severe eosinophilic asthma. Atopic dermatitis (AD) and asthma have similar inflammatory features. New biologic treatments such as the anti-IL22, Fezakinumab (FZ), have been introduced. <b>Aims:</b> To determine whether the signature of differentially-expressed genes in lesional AD skin tissue following treatment with FZ are present in the blood and airway transcriptomics of asthma patients in the U-BIOPRED cohort. <b>Methods:</b> We used FZ response signatures with keratinocyte,T-cell, and dendritic cell genes significantly downregulated in AD lesional tissue after 12 week treatment1. The enrichment scores (ES) of FZ response signatures was obtained by Gene Set Variation Analysis using the transcriptome of bronchial brushings (BB), sputum (S) and blood (B) of mild-moderate and severe asthma patients (n=323) and healthy controls (n=87). <b>Results:</b> FZ response signatures were significantly enriched in the blood of asthmatics versus healthy subjects (p&lt;0.05)(Fig&nbsp;1). Interestingly, FZ response signature defined in high-IL22 AD phenotype improved ES in high IL22 asthma phenotype for BB,S and B. <b>Conclusions:</b> A subset of asthmatics may respond to anti-IL-22 antibody therapy. While the role of IL-22 in asthma remains to be elucidated, our study indicates that AD and a subset of asthma patients may share IL-22 pathways. <b>Reference:</b> Brunner P etal. JACI 2019 143(142-154)